DESCRIPTION: In current medical treatment of atherosclerosis, a stent is placed for flow-limiting (i.e., >60% stenosis) plaques diagnosed by X-ray based angiography. Revascularization by stenting a flow-limiting coronary artery stenosis has profoundly improved survival. Plaque that is not flow-limiting and thus not stented, however, can be unstable and vulnerable to rupture, which is the major cause of acute myocardial infarction. Currently, no imaging tools exist to diagnose these non-flow-limiting yet potentially vulnerable plaques. The long-term goal of our project is to develop an intravascular vibrational photoacoustic (IVPA) catheter for clinica detection of vulnerable plaques. The objective of this R01 application is to demonstrate an IVPA system for real-time in vivo intravascular visualization of atherosclerotic plaque in a clinically relevant Ossabaw pig model. An interdisciplinary team has been assembled to approach this objective. Dr. Ji-Xin Cheng (Purdue University) is an expert in development and applications of vibrational spectral imaging. Dr. Michael Sturek (Indiana University School of Medicine) is an expert in cardiovascular research. Dr. Qifa Zhou (University of Southern California) is an expert in design and fabrication of ultrasound transducers. Consultant Art Coffey (M.D. in IU Health) is a cardiovascular surgeon who will provide clinical input on the IVPA catheter design. Our central hypothesis is that a high-speed IVPA system allows for in vivo assessment of lipid-rich, inflammatory plaques in an arterial wall. This hypothesis will be tested by 3 Specific Aims. (1) Develop a high-speed IVPA system and demonstrate real-time dual-modality PA/US sensing of an intact atherosclerotic artery in vitro. (2) Differentiate cholesterol crystal (CC) from cholesteol ester (CE)-rich lipid droplets inside an intact artery by spectral analysis of optically induced ultrasound signals. (3) Validate the IVPA system for in vivo assessment of atherosclerotic plaques in an Ossabaw swine model. Successful development of the IVPA system will be able to guide appropriate treatment, e.g. stent deployment, for the lipid-laden, unstable plaque that is not detectable by current intravascular catheters, thus potentially a life-saving technology.